NCT03596827

Brief Summary

The existing diarrhoeagenic Escherichia coli (E. coli) challenge model is already suitable for dietary interventions in its current form, targeted to impact on the immediate clinical symptoms upon E. coli infection. In order to make the model also suitable for dietary interventions that are aimed at support of the protective response against reinfection, the immune response triggered by the primary infection should be suboptimal. The MIRRE pilot study is set up to determine how much the primary inoculation dose of diarrheagenic E. coli should be lowered in order to result in a reduced protective response upon a secondary infection.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Sep 2018

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 12, 2018

Completed
12 days until next milestone

First Posted

Study publicly available on registry

July 24, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

September 26, 2018

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 13, 2018

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2019

Completed
Last Updated

March 20, 2019

Status Verified

March 1, 2019

Enrollment Period

2 months

First QC Date

July 12, 2018

Last Update Submit

March 18, 2019

Conditions

Diarrhea

Keywords

DiarrheaGastroenteritisBacterial InfectionsEscherichia Coli InfectionsE.coli

Outcome Measures

Primary Outcomes (1)

  • Change in specific antibody titer

    Serum IgG-CFA/II antibody levels in relation to clinical symptoms at second E.coli inoculation

    Day 14,21,28 and Day 35,42,49

Secondary Outcomes (4)

  • Change in percentage of faecal wet weight from baseline

    Day 11,12 and Day 15-17. Day 33,34 and 36-38

  • Change in Stool consistency (Bristol stool scale) from baseline

    Day 11-17 and Day 32-38

  • Change in Stool frequency from baseline

    Day 11-17 and Day 32-38

  • Change in incidence, duration and severity of Gastro-intestinal symptoms from baseline

    Day 11-17 and Day 32-38

Study Arms (5)

1E10 CFU Escherichia coli (E. coli)

ACTIVE COMPARATOR

At day 14, after a standardized evening meal and overnight fast, subjects receive a single oral dose of 1E10 CFU of the attenuated diarrhoeagenic E. coli strain E1392-75-2A. At day 35, after a standardized evening meal and overnight fast, all subjects receive a second inoculation 1E10 CFU of the diarrhoeagenic E. coli.

Biological: E. coli strain E1392-75-2A dose 1E10 CFU

1E9 CFU Escherichia coli (E. coli)

EXPERIMENTAL

At day 14, after a standardized evening meal and overnight fast, subjects receive a single oral dose of 1E9 CFU of the attenuated diarrhoeagenic E. coli strain E1392-75-2A. At day 35, after a standardized evening meal and overnight fast, all subjects receive a second inoculation 1E10 CFU of the diarrhoeagenic E. coli.

Biological: E. coli strain E1392-75-2A dose 1E9 CFU

1E8 CFU Escherichia coli (E. coli)

EXPERIMENTAL

At day 14, after a standardized evening meal and overnight fast, subjects receive a single oral dose of 1E8 CFU of the attenuated diarrhoeagenic E. coli strain E1392-75-2A. At day 35, after a standardized evening meal and overnight fast, all subjects receive a second inoculation 1E10 CFU of the diarrhoeagenic E. coli.

Biological: E. coli strain E1392-75-2A dose 1E8 CFU

1E7 CFU Escherichia coli (E. coli)

EXPERIMENTAL

At day 14, after a standardized evening meal and overnight fast, subjects receive a single oral dose of 1E7 CFU of the attenuated diarrhoeagenic E. coli strain E1392-75-2A. At day 35, after a standardized evening meal and overnight fast, all subjects receive a second inoculation 1E10 CFU of the diarrhoeagenic E. coli.

Biological: E. coli strain E1392-75-2A dose 1E7 CFU

1E6 CFU Escherichia coli (E. coli)

EXPERIMENTAL

At day 14, after a standardized evening meal and overnight fast, subjects receive a single oral dose of 1E6 CFU of the attenuated diarrhoeagenic E. coli strain E1392-75-2A. At day 35, after a standardized evening meal and overnight fast, all subjects receive a second inoculation 1E10 CFU of the diarrhoeagenic E. coli.

Biological: E. coli strain E1392-75-2A dose 1E6 CFU

Interventions

E. coli strain E1392-75-2A dose 1E10 CFUBIOLOGICAL

Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain

1E10 CFU Escherichia coli (E. coli)
E. coli strain E1392-75-2A dose 1E9 CFUBIOLOGICAL

Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain

1E9 CFU Escherichia coli (E. coli)
E. coli strain E1392-75-2A dose 1E8 CFUBIOLOGICAL

Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonization Factor Antigen II (CFA/II) and provides 75% protection against challenge with an LT, ST, CFA/II strain

1E8 CFU Escherichia coli (E. coli)
E. coli strain E1392-75-2A dose 1E7 CFUBIOLOGICAL

Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonizat

1E7 CFU Escherichia coli (E. coli)
E. coli strain E1392-75-2A dose 1E6 CFUBIOLOGICAL

Diarrhoeagenic E. coli strain E1392/75-2A serotype O6:H16 belongs to Pathogen class 2 . The strain has a deletion of genes encoding the heat-labile (LT) and heat-stable (ST) toxins and can not produce any toxins. However, it continues to express Colonizat

1E6 CFU Escherichia coli (E. coli)

Eligibility Criteria

Age18 Years - 55 Years
Sexmale(Gender-based eligibility)
Gender Eligibility DetailsGender identity is self-reported by the subjects through a questionnaire.
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • In order to be eligible to participate in this study, a subject must meet all of the following criteria:
  • Male
  • Age between 18 and 55 years.
  • BMI ≥18.5 and ≤30.0 kg/m2.
  • Healthy as assessed by the NIZO health questionnaire.
  • Ability to follow Dutch verbal and written instructions.
  • Availability of internet connection.
  • Signed informed consent.
  • Willing to accept disclosure of the financial benefit of participation in the study to the authorities concerned.
  • Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years.
  • Willing to comply with study procedures, including collection of stool and blood samples.
  • Willingness to abstain from high calcium containing products.
  • Willingness to abstain from alcoholic beverages three days before, during and for 4 days after diarrheagenic E. coli challenge.
  • Willingness to abstain from medications that contain acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs, (OTC) antacids and antimotility agents (eg, loperamide) on the three days before, during and for 4 days after diarrheagenic E. coli challenge.
  • Willingness to abstain from probiotics and prebiotic/fibers starting from runin and during the whole study.
  • +1 more criteria

You may not qualify if:

  • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  • Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus infection (HIV).
  • Disease of the GI tract, liver, gall bladder, kidney, thyroid gland (self-reported), except for appendicitis.
  • Vaccination for, or ingestion of ETEC or E coli heat labile toxin, including E. coli challenge studies at NIZO.
  • Evidence of current excessive alcohol consumption (\>4 consumptions/day or \>20 consumptions/week) or drug (ab)use, and not willing/able to stop this during the study.
  • Known allergy to the following antibiotics: ciprofloxacin, trimethoprim, sulfamethoxazole, and penicillins.
  • Reported average stool frequency of \>3 per day or \<1 per 2 days.
  • Use of immunosuppressive drugs (e.g. cyclosporine, azathioprine, systemic corticosteroids, antibodies).
  • Vegans.
  • Mental status that is incompatible with the proper conduct of the study.
  • Not having a general practitioner, not allowing disclosure of participation to the general practitioner or not allowing to inform the general practitioner about abnormal results.
  • Participation in any clinical trial including blood sampling and/or administration of substances starting 1 month prior to study start and during the entire study.
  • Personnel that is part of the study team at NIZO, their partner and their first and second degree relatives.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

NIZO Food Research

Ede, Gelderland, 6718ZB, Netherlands

Location

Related Publications (2)

  • Bovee-Oudenhoven IM, Lettink-Wissink ML, Van Doesburg W, Witteman BJ, Van Der Meer R. Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium. Gastroenterology. 2003 Aug;125(2):469-76. doi: 10.1016/s0016-5085(03)00884-9.

    PMID: 12891550BACKGROUND

  • Ten Bruggencate SJ, Girard SA, Floris-Vollenbroek EG, Bhardwaj R, Tompkins TA. The effect of a multi-strain probiotic on the resistance toward Escherichia coli challenge in a randomized, placebo-controlled, double-blind intervention study. Eur J Clin Nutr. 2015 Mar;69(3):385-91. doi: 10.1038/ejcn.2014.238. Epub 2014 Nov 5.

    PMID: 25369827BACKGROUND

Related Links

MeSH Terms

Conditions

DiarrheaGastroenteritisBacterial InfectionsEscherichia coli Infections

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsGastrointestinal DiseasesDigestive System DiseasesBacterial Infections and MycosesInfectionsEnterobacteriaceae InfectionsGram-Negative Bacterial Infections

Study Officials

  • Melle van Schaik

    NIZO Food Research

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: The MIRRE pilot study is a randomized, double-blind dose-response, parallel human infection study in 30 healthy adults
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 12, 2018

First Posted

July 24, 2018

Study Start

September 26, 2018

Primary Completion

November 13, 2018

Study Completion

February 28, 2019

Last Updated

March 20, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)